P531: AN OBSERVATIONAL, MULTICENTER, RETROSPECTIVE ANALYSIS OF PATIENTS WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM TREATED WITH TAGRAXOFUSP IN THE EUROPEAN EXPANDED ACCESS PROGRAM
Authors: M. Herling, E. Deconinck, M. Anant, D. Manteigas, M. Riggi, E. Angelucci
Journal: HemaSphere (2022)

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive hematologic malignancy, with poor prognosis (median age 67 yr). It is characterized by clonal expansion of plasmacytoid dendritic tumor cells expressing specific markers including the interleukin-3 receptor alpha (CD123). Primary sites are skin and bone marrow, followed by peripheral blood, lymph nodes, viscera, and central nervous system. Tagraxofusp (TAG), a CD123-targeted therapy, was approved by the European Medicines Agency on 07.01.2021. In 08.2019, a Global Expanded Access Program (EAP) was implemented to provide access to patients (pts) prior to regulatory authorization of TAG in real-world practice. Aims: We conducted a European multicenter non-interventional, retrospective analysis of BPDCN pts treated with TAG. Main objectives were rates of complete response, and incidence and severity of capillary leak syndrome (CLS). Secondary outcomes included rate of pts bridged to stem cell transplantation, progression-free survival, and overall survival, safety of TAG measured by the incidence and severity of adverse events (AEs), and number of TAG doses administered in each cycle. Methods: The main inclusion criterion was diagnosis of BPDCN, confirmed by hematopathology with established marker panels (including CD123). The physician who signed the supply form of TAG in each participating center informed the pts on their treatment. Training of the physicians, nurses, and pharmacists was mandatory before delivering the treatment. The analysis included all pts enrolled in the European EAP from 08.2019 to 12.2021. Pts received TAG intravenous infusions, at 12 mcg/kg once daily on days 1–5 (up to day 10 allowed) of a 21-day cycle. Hospitalization was required only for the first cycle (subsequent cycles were allowed to be administered in an outpatient setting). Results: Overall, 76 adult (median age 64 yr, range 21–85 yr) and 4 pediatric pts (1, 4, 14, and 16 yr) were included across 57 European centers: Germany 18 centers, France 17, Italy 9, Switzerland 5, United Kingdom 4, Spain 3, and Austria 1. Most pts were male (78%), representing real-world distribution. Sixty-three pts received first-line TAG and 17 pts as second or further line of treatment. The median number of cycles (based on the number of treatments delivered for the TAG EAP supply of each 21-day cycle) was 2.5 (range 1–8) in first line and 2.6 (range 1–13) cycles in second-line and further pts, respectively. No deaths due to CLS were reported. The analysis is still ongoing at the time of abstract finalization; complementary data on safety, efficacy, number of pts transplanted, and time-related parameters will be reported at the meeting. Summary/Conclusion: The is the largest retrospective analysis of real-world clinical practice outside of a clinical trial in BPDCN pts treated with TAG. The EAP was carefully followed in all 57 centers with initial training provided to the multidisciplinary teams before treatment initiation. This is thought to have positively affected prevention and management of CLS and other grade 3–4 AEs; no death related to CLS occurred. The preliminary results confirm the feasibility and safety of TAG, allowing the administration also in elderly pts, with manageable safety. In fact, AEs mainly occurred in cycle 1 in an inpatient setting, with similar rates and severity in older vs younger pts. Baseline characteristics did not appear to predispose pts to different treatment-related AEs.